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Decoding gene regulation in the fly brain

Authors :
Jasper Janssens
Sara Aibar
Ibrahim Ihsan Taskiran
Joy N. Ismail
Alicia Estacio Gomez
Gabriel Aughey
Katina I. Spanier
Florian V. De Rop
Carmen Bravo González-Blas
Marc Dionne
Krista Grimes
Xiao Jiang Quan
Dafni Papasokrati
Gert Hulselmans
Samira Makhzami
Maxime De Waegeneer
Valerie Christiaens
Tony Southall
Stein Aerts
Publication Year :
2022
Publisher :
NATURE PORTFOLIO, 2022.

Abstract

The Drosophila brain is a frequently used model in neuroscience. Single-cell transcriptome analysis1-6, three-dimensional morphological classification7 and electron microscopy mapping of the connectome8,9 have revealed an immense diversity of neuronal and glial cell types that underlie an array of functional and behavioural traits in the fly. The identities of these cell types are controlled by gene regulatory networks (GRNs), involving combinations of transcription factors that bind to genomic enhancers to regulate their target genes. Here, to characterize GRNs at the cell-type level in the fly brain, we profiled the chromatin accessibility of 240,919 single cells spanning 9 developmental timepoints and integrated these data with single-cell transcriptomes. We identify more than 95,000 regulatory regions that are used in different neuronal cell types, of which 70,000 are linked to developmental trajectories involving neurogenesis, reprogramming and maturation. For 40 cell types, uniquely accessible regions were associated with their expressed transcription factors and downstream target genes through a combination of motif discovery, network inference and deep learning, creating enhancer GRNs. The enhancer architectures revealed by DeepFlyBrain lead to a better understanding of neuronal regulatory diversity and can be used to design genetic driver lines for cell types at specific timepoints, facilitating their characterization and manipulation. ispartof: NATURE vol:601 issue:7894 pages:630-+ ispartof: location:England status: published

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....87607de00f68769629154bd50c4b66a7